Assessment of clinical trial protocols for pathology content using the SPIRIT-Path guidelines highlights areas for improvement

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence-based recommendations for the minimum content of clinical trial protocols. The Cellular Molecular Pathology Initiative, hosted by the UK National Cancer Research Institute, developed an extension, SPIRIT-Path, describing how to effectively incorporate pathology support into clinical trial protocols. The current study assessed the inclusion of SPIRIT-Path items in protocols of active clinical trials. Publicly available clinical trial protocols were identified for assessment against the new guidelines using a single UK hospital as the ‘test site’. One hundred and ninety interventional clinical trials were identified as receiving support from the pathology department. However, only 38 had publicly available full trial protocols (20%) and following application of the inclusion/exclusion criteria, 19 were assessed against the SPIRIT-Path guidelines. The reviewed clinical trial protocols showed some areas of compliance and highlighted other items that were inadequately described. The latter lacked information about the individuals responsible for the pathology content of the trial protocol, how pathology activities and roles were organised in the trial, where the laboratory work would be carried out, and the accreditation status of the laboratory. Only one trial had information specific to digital pathology, a technology certain to become more prevalent in the future. Adoption of the SPIRIT-Path checklist will facilitate comprehensive trial protocols that address all the key cellular and molecular pathology aspects of interventional clinical trials. This study highlights once again the lack of public availability of trial protocols. Full trial protocols should be available for scrutiny by the scientific community and the public who participate in the studies, increasing the transparency of clinical trial activity and improving quality

Modelling the bimodal distribution of indoor gamma-ray dose-rates in Great Britain

Gamma radiation from naturally occurring sources (including directly ionizing cosmic-rays) is a major component of background radiation. An understanding of the magnitude and variation of doses from these sources is important, and the ability to predict them is required for epidemiological studies. In the present paper, indoor measurements of naturally occurring gamma-rays at representative locations in Great Britain are summarized. It is shown that, although the individual measurement data appear unimodal, the distribution of gamma-ray dose-rates when averaged over relatively small areas, which probably better represents the underlying distribution with inter-house variation reduced, appears bimodal. The dose-rate distributions predicted by three empirical and geostatistical models are also bimodal and compatible with the distributions of the areally averaged dose-rates. The distribution of indoor gamma-ray dose-rates in the UK is compared with those in other countries, which also tend to appear bimodal (or possibly multimodal). The variation of indoor gamma-ray dose-rates with geology, socio-economic status of the area, building type, and period of construction are explored. The factors affecting indoor dose-rates from background gamma radiation are complex and frequently intertwined, but geology, period of construction, and socio-economic status are influential; the first is potentially most influential, perhaps, because it can be used as a general proxy for local building materials. Various statistical models are tested for predicting indoor gamma-ray dose-rates at unmeasured locations. Significant improvements over previous modelling are reported. The dose-rate estimates generated by these models reflect the imputed underlying distribution of dose-rates and provide acceptable predictions at geographical locations without measurements

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Towards Machine Wald

The past century has seen a steady increase in the need of estimating and predicting complex systems and making (possibly critical) decisions with limited information. Although computers have made possible the numerical evaluation of sophisticated statistical models, these models are still designed \emph{by humans} because there is currently no known recipe or algorithm for dividing the design of a statistical model into a sequence of arithmetic operations. Indeed enabling computers to \emph{think} as \emph{humans} have the ability to do when faced with uncertainty is challenging in several major ways: (1) Finding optimal statistical models remains to be formulated as a well posed problem when information on the system of interest is incomplete and comes in the form of a complex combination of sample data, partial knowledge of constitutive relations and a limited description of the distribution of input random variables. (2) The space of admissible scenarios along with the space of relevant information, assumptions, and/or beliefs, tend to be infinite dimensional, whereas calculus on a computer is necessarily discrete and finite. With this purpose, this paper explores the foundations of a rigorous framework for the scientific computation of optimal statistical estimators/models and reviews their connections with Decision Theory, Machine Learning, Bayesian Inference, Stochastic Optimization, Robust Optimization, Optimal Uncertainty Quantification and Information Based Complexity.Comment: 37 page

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

Genuine Correlations of Like-Sign Particles in Hadronic Z0 Decays

Correlations among hadrons with the same electric charge produced in Z0 decays are studied using the high statistics data collected from 1991 through 1995 with the OPAL detector at LEP. Normalized factorial cumulants up to fourth order are used to measure genuine particle correlations as a function of the size of phase space domains in rapidity, azimuthal angle and transverse momentum. Both all-charge and like-sign particle combinations show strong positive genuine correlations. One-dimensional cumulants initially increase rapidly with decreasing size of the phase space cells but saturate quickly. In contrast, cumulants in two- and three-dimensional domains continue to increase. The strong rise of the cumulants for all-charge multiplets is increasingly driven by that of like-sign multiplets. This points to the likely influence of Bose-Einstein correlations. Some of the recently proposed algorithms to simulate Bose-Einstein effects, implemented in the Monte Carlo model PYTHIA, are found to reproduce reasonably well the measured second- and higher-order correlations between particles with the same charge as well as those in all-charge particle multiplets.Comment: 26 pages, 6 figures, Submitted to Phys. Lett.

Psychosocial Treatment of Children in Foster Care: A Review

A substantial number of children in foster care exhibit psychiatric difficulties. Recent epidemiologi-cal and historical trends in foster care, clinical findings about the adjustment of children in foster care, and adult outcomes are reviewed, followed by a description of current approaches to treatment and extant empirical support. Available interventions for these children can be categorized as either symptom-focused or systemic, with empirical support for specific methods ranging from scant to substantial. Even with treatment, behavioral and emotional problems often persist into adulthood, resulting in poor functional outcomes. We suggest that self-regulation may be an important mediat-ing factor in the appearance of emotional and behavioral disturbance in these children